tbuckley/cabot-search huggingface dataset:
CAR-T Cell Therapy for Classical Hodgkin Lymphoma
Authors: Mikalai Katsin, Dmitri Dormeshkin, Alexander Meleshko, Alexandr Migas, Simon Dubovik, Natalya Konoplya
Journal: HemaSphere (2023)

Classical Hodgkin lymphoma (cHL) is a malignancy characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells within a complex tumor microenvironment (TME). Despite advances in conventional therapies, a subset of cHL patients experience relapse or refractory disease, necessitating the exploration of novel treatment strategies. Chimeric antigen receptor T cell (CAR-T cell) therapy has emerged as a promising approach for the management of cHL, harnessing the power of genetically modified T cells to recognize and eliminate tumor cells. In this article, we provide an overview of the pathogenesis of cHL, highlighting the key molecular and cellular mechanisms involved. Additionally, we discuss the rationale for the development of CAR-T cell therapy in cHL, focusing on the identification of suitable targets on HRS cells (such as CD30, CD123, LMP1, and LMP2A), clonotypic lymphoma initiating B cells (CD19, CD20), and cells within the TME (CD123, CD19, CD20) for CAR-T cell design. Furthermore, we explore various strategies employed to enhance the efficacy and safety of CAR-T cell therapies in the treatment of cHL. Finally, we present an overview of the results obtained from clinical trials evaluating the efficacy of CAR-T cell therapies in cHL, highlighting their potential as a promising therapeutic option. Collectively, this article provides a comprehensive review of the current understanding of cHL pathogenesis and the rationale for CAR-T cell therapy development, offering insights into the future directions of this rapidly evolving field.
PRESSING Need of Precision Care in HER2-Positive Colorectal Cancer: The ELEPHANT in the Room
Authors: Kanwal P.S. Raghav, Jonathan M. Loree, Scott Kopetz
Journal: Clinical Cancer Research (2023)

Summary. Although dual HER2 inhibition has shown promising clinical activity in patients with RAS wild-type HER2-positive metastatic colorectal cancer, predictive biomarkers of response/resistance are less well characterized. Activating HER2/RTK/MAPK genomic alterations appears to blunt the clinical benefit of dual anti-HER2 therapy and may hold a potential albeit partial role in patient selection.See related article by Randon et al., p. xxx
Perceptions of Use of Names, Recognition of Roles, and Teamwork After Labeling Surgical Caps
Authors: Becky J. Wong, Aussama K. Nassar, Michelle Earley, Ling Chen, Teresa Roman-Micek, Samuel H. Wald, Tait D. Shanafelt, Sara N. Goldhaber-Fiebert
Journal: JAMA Network Open (2023)

Communication failures in perioperative areas are common and have negative outcomes for both patients and clinicians. Names and roles of teammates are difficult to remember or discern contributing to suboptimal communication, yet the utility of labeled surgical caps with names and roles for enhancing perceived teamwork and connection is not well studied.
Phase I/IIa Trial in Advanced Pancreatic Ductal Adenocarcinoma Treated with Cytotoxic Drug-Packaged, EGFR-Targeted Nanocells and Glycolipid-Packaged Nanocells
Authors: Vinod Ganju, Gavin Marx, Scott Pattison, Nancy B. Amaro-Mugridge, Jing-Ting Zhao, Bryan R.G. Williams, Jennifer A. MacDiarmid, Himanshu Brahmbhatt
Journal: Clinical Cancer Research (2023)

Abstract Purpose: We assessed the safety and efficacy of an EGFR-targeted, super-cytotoxic drug, PNU-159682-packaged nanocells with α-galactosyl ceramide-packaged nanocells (E-EDV-D682/GC) in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who had exhausted all treatment options. Patients and Methods: ENG9 was a first-in-man, single-arm, open-label, phase I/IIa, dose-escalation clinical trial. Eligible patients had advanced PDAC, Eastern Cooperative Oncology Group status 0 to 1, and failed all treatments. Primary endpoints were safety and overall survival (OS). Results: Of 25 enrolled patients, seven were withdrawn due to rapidly progressive disease and one patient withdrew consent. All 25 patients were assessed for toxicity, 24 patients were assessed for OS, which was also assessed for 17 patients completing one treatment cycle [evaluable subset (ES)]. Nineteen patients (76.0%) experienced at least one treatment-related adverse event (graded 1 to 2) resolving within hours. There were no safety concerns, dose reductions, patient withdrawal, or treatment-related deaths. Median OS (mOS) was 4.4 months; however, mOS of the 17 ES patients was 6.9 months [208 days; range, 83–591 days; 95.0% confidence interval (CI), 5.6–10.3 months] and mOS of seven patients who did not complete one cycle was 1.8 months (54 days; range, 21–72; 95.0% CI, 1.2–2.2 months). Of the ES, 47.1% achieved stable disease and one partial response. Ten subjects in the ES survived over 6 months, the longest 19.7 months. During treatments, 82.0% of the ES maintained stable weight. Conclusions: E-EDV-D682/GC provided significant OS, minimal side effects, and weight stabilization in patients with advanced PDAC. Advanced PDAC can be safely treated with super-cytotoxic drugs via EnGeneIC Dream Vectors to overcome multidrug resistance.
Decoding the nodular melanoma subtype- what about genetics?
Authors: Clio Dessinioti, Alexander J Stratigos
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Decoding the nodular melanoma subtype: what about genetics? Get access Clio Dessinioti, Clio Dessinioti Conceptualization, Writing - original draft, Writing - review & editing Skin Cancer and Melanoma Unit, 1st Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece https://orcid.org/0000-0002-4832-3410 Search for other works by this author on: Oxford Academic Google Scholar Alexander J Stratigos Alexander J Stratigos Conceptualization, Writing - original draft, Writing - review & editing Skin Cancer and Melanoma Unit, 1st Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece Correspondence: Alexander J. Stratigos. Email: alstrat2@gmail.com https://orcid.org/0000-0002-4989-9075 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad445, https://doi.org/10.1093/bjd/ljad445 Published: 17 November 2023 Article history Received: 30 October 2023 Revision received: 05 November 2023 Accepted: 05 November 2023 Published: 17 November 2023 Corrected and typeset: 06 January 2024
Nuclear‐Targeted Nanostrategy Regulates Spatiotemporal Communication for Dual Antitumor Immunity
Authors: Ben Wang, Zhi‐Chao Hu, Li‐Jie Chen, Hai‐Feng Liang, Hong‐Wei Lu, Qing Chen, Bing Liang, Abudula Aji, Jian Dong, Qi‐Wei Tian, Li‐Bo Jiang, Feng‐Feng Xue
Journal: Advanced Healthcare Materials (2023)

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8+ T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence.
Near‐Infrared Light‐Triggered Thermoresponsive Pyroptosis System for Synergistic Tumor Immunotherapy
Authors: Guoqing Zhu, Pan Zheng, Man Wang, Yulin Xie, Qianqian Sun, Minghong Gao, Chunxia Li
Journal: Advanced Healthcare Materials (2023)

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as
Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates
Authors: Xiaohui Chen, Meichun Gao, Yongzhen Xia, Xin Wang, Jingbo Qin, Hongying He, Weirong Liu, Xiaowei Zhang, Shuangzhou Peng, Zhiping Zeng, Ying Su, Xiaokun Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor cells. The pro-death effect of Nur77 can be regulated by its interaction with Bcl-2, resulting in conversion of Bcl-2 from a survival to killer. As Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy, targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer therapeutics. Here, we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 pathway.
LTBK-09. RESULTS OF BMX-HGG STUDY: A MULTI-INSTITUTIONAL, RANDOMIZED PHASE 2 CLINICAL TRIAL OF CONCURRENT CHEMORADIATION WITH OR WITHOUT BMX-001 IN PATIENTS WITH NEWLY DIAGNOSED HIGH GRADE GLIOMA
Authors: Katherine Peters, Adam Cohen, Nicholas Butowski, John Villano, Joe Mendez, Pierre Giglio, Tresa McGranahan, Chi Zhang, Jacob Smeltzer, Shahzad Raza, Burt Nabors, Mina Lobbous, James Herndon, Evan Buckley, David MacLeod, Sara Penchev, David Silberstein, Ines Batinic-Haberle, Ivan Spasojevic, Shayne Gad, David Radoff, Daniel Barboriak, James Crapo
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Standard treatment for high grade glioma (HGG) remains neurosurgical resection followed by concurrent radiation therapy (RT) and temozolomide (TMZ). Overall survival (OS) for GBM is roughly 12-16 months. RT is associated with cognitive and quality of life (QoL) impairments. Advances are needed to improve OS while mitigating injury to the normal brain. BMX-001 is a novel metalloporphyrin that radiosensitizes cancer cells and radioprotects normal tissue. METHODS This multi-institutional, open-label, phase 2 trial randomized newly diagnosed HGG patients to receive RT/TMZ with or without BMX-001 (NCT02655601). Both arms received 6 weeks RT/TMZ (75 mg/m2). BMX-001 was administered as a loading dose of 28 mg sc before RT, followed by 14 mg twice weekly for 8 weeks. Randomization was stratified by tumor grade and institution. Key eligibility criteria include histologically confirmed HGG, age ≥ 18 years, and KPS ≥ 70%. The primary endpoint was OS. Key secondary/exploratory outcomes included cognition, QoL, and white matter integrity using advanced imaging. OS evaluation occurred after 84 deaths when a 1-tailed logrank test (α=0.2) had 90% power to detect a hazard ratio of 0.63. Two interim analyses and a final analysis were conducted using an O’Brien-Fleming stopping boundary. RESULTS Of the 160 patients randomized, 72.5% had GBM, and 62.5% were male. Analyses focused on 145 patients who completed RT/TMZ (74 with BMX-001, 71 without BMX-001). Median OS of BMX-001+RT/TMZ group (31.3 [95% CI, 21.6, not reached] months) was longer than RT/TMZ group (24.7 [95% CI, 19.6-32.6] months), HR=0.735; p=0.079 (significant at the predefined α level). Common toxicities (Grade 1-2) attributed to BMX-001 were injection site reactions (64), tachycardia (24), and pruritus (17) with no related Grade 4-5. Diffusion tensor MR imaging indicated mitigation of dose-related white matter damage in BMX-001+RT/TMZ group. CONCLUSIONS BMX-001 is safe, and there is improved OS in HGG patients receiving BMX-001.
Low Greenhouse Gas Emission Self-Selective Diets and Risk of Metabolic Syndrome in Adults 40 and Older: A Prospective Cohort Study in South Korea
Authors: Li-Juan Tan, Sangah Shin
Journal: Environmental Health Perspectives (2023)

The food system accounts for ∼40% of human-generated greenhouse gas (GHG) emissions. Meanwhile, daily diet selection also impacts human nutrition status and health.This study aimed to use the alternate Mediterranean Diet (aMED) score to evaluate the quality of a low-GHG emission diet and the association with risk of developing metabolic syndrome (MetS).A total of 41,659 healthy participants without MetS 40 y of age or older were selected from the Health Examinees Study, an ongoing cohort study in South Korea from 2004. A dietary GHG emissions database was compiled following a national project and literature review. MetS was defined according to the Adult Treatment Panel III criteria of the National Cholesterol Education Program. The participants were grouped into quintiles based on 2,000 kcal-standardized daily diet-GHG emissions (Q1: the lowest energy-adjusted diet-GHG emissions). A multivariable logistic regression model was used to analyze the risk for MetS at follow-up. The aMED score was used to assess the diet quality of the different diet-related GHG emission groups.Females with lower energy-adjusted diet-related GHG emissions had significantly lower risks of developing MetS (p=0.0043) than those with the highest energy-adjusted diet-related GHG emissions. In addition, the Q1 group, in comparison with the other groups, had a higher aMED score (3.02 for males and 3.00 for females), which indicated that the participants in this group had a diet that more closely matched the Mediterranean diet.These findings provide a reference for dietary guidance and other policies aimed toward improving dietary intake and reducing diet-related GHG emissions in South Korea and worldwide. https://doi.org/10.1289/EHP12727.
Contents
Authors: Anika Kumar, D Claire Miller, Yuwei Sun, Benjamin Arnold, Nisha Acharya, Yunhe Song, Fei Li, Rachel Chong, Wei Wang, An Ran, Fengbin Lin, Peiyuan Wang, Zhenyu Wang, Jingwen Jiang, Kangjie Kong, Ling Jin, Meiling Chen, Jian Sun, Deming Wang, Clement Tham, Dennis Lam, Linda Zangwill, Robert Weinreb, Tin Aung, Jost Jonas, Kyoko Ohno-Matsui, Ching-Yu Cheng, Neil Bressler, Xiaodong Sun, Carol Cheung, Shida Chen, Xiulan Zhang, Salvatore Grisanti, Friederike Schindler, Hartmut Merz, Vinodh Kakkassery, Rebecca Sonntag, Ayseguel Tura, Avital Lily, Okrent Smolar, Hetal Ray, Michael Dattilo, Walid Bouthour, Gabriele Berman, Jason Peragallo, Sachin Kedar, Andrew Pendley, James Greene, Matthew Keadey, David Wright, Beau Bruce, Nancy Newman, Christine Yergeau, Razek Coussa, Catherine Argyriou, Robert Koenekoop, Nancy Braverman, Malena Daich Varela, Giovanni Conti, Samantha Malka, Veronika Vaclavik, Omar Mahroo, Andrew Webster, Viet Tran, Michel Michaelides
Journal: Ophthalmology (2023)
Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects
Authors: Zehao Jing, Wanqiong Yuan, Jiedong Wang, Renhua Ni, Yu Qin, Zhinan Mao, Feng Wei, Chunli Song, Yufeng Zheng, Hong Cai, Zhongjun Liu
Journal: Bioactive Materials (2023)

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both
Zn-Fe primary battery-enabled controlled hydrogen release in stomach for improving insulin resistance in obesity-associated type 2 diabetes
Authors: Boyan Liu, Peixun Lv, Xiaoyi Zhang, Chao Xia, Xinru Liu, Jingyu Liu, Junli Xue, Qianjun He, Shucun Qin
Journal: Bioactive Materials (2023)

Chronic systemic inflammation in obesity-associated type 2 diabetes (T2D) is a key inducing factor of insulin resistance (IR). Hydrogen molecule (H2) has been proved to be a safe and effective anti-inflammatory agent, but conventional H2 administration methods cannot provide a high dosage and a long duration of H2 treatment in IR-related tissues and thus lead to limited therapeutic efficacies. We here propose a new strategy of controlled H2 release to match the time window of gastric emptying for maximizing the bioavailability and therapeutic outcome of H2. This work enhances the hydrolysis rate of Zn by constructing a Zn-Fe primary-battery micro-/nano-structure, and the H2-releasing rate is adjusted by tuning the ratio of Zn to Fe. The Zn-Fe micro-/nano-structure is orally administrated once daily to alleviate obesity-associated T2D in a leptin-deficient (ob/ob) mouse model. The H2 generation time of the Zn-Fe primary-battery micro-/nano-structure with the Fe/Zn ratio of 1:100 in gastric acid is about 3 h, just matching with the time window of gastric emptying in mice. In vivo monitoring results show that H2 generated by Zn-Fe micro-/nano-structure in stomach can effectively accumulate in major IR-sited tissues including liver, adipose tissue, and skeletal muscle at a high dose for a relatively long time compared to H2-rich water drinking. Oral administration of Zn-Fe micro-/nano-structure at 200 mg/kg body weight has realized an efficient IR improvement and remarkably ameliorated systemic inflammation in ob/ob mice. In addition, a high-dose administration of Zn-Fe shows no visible toxicity in mice. This work provides a new strategy to maximize the outcome of hydrogen therapy.
Bridging the Gap—Thermofluidic Designs for Precision Bioelectronics
Authors: Jingcheng Ma, Aman Majmudar, Bozhi Tian
Journal: Advanced Healthcare Materials (2023)

Abstract Bioelectronics, the merging of biology and electronics, can monitor and modulate biological behaviors across length and time scales with unprecedented capability. Current bioelectronics research largely focuses on devices’ mechanical properties and electronic designs. However, the thermofluidic control is often overlooked, which is noteworthy given the discipline's importance in almost all bioelectronics processes. It is believed that integrating thermofluidic designs into bioelectronics is essential to align device precision with the complexity of biofluids and biological structures. This perspective serves as a mini roadmap for researchers in both fields to introduce key principles, applications, and challenges in both bioelectronics and thermofluids domains. Important interdisciplinary opportunities for the development of future healthcare devices and precise bioelectronics will also be discussed.
Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials
Authors: Anke de Haan, Richard Meiser-Stedman, Markus A Landolt, Isla Kuhn, Melissa J Black, Kristel Klaus, Shivam D Patel, David J Fisher, Christina Haag, Obioha C Ukoumunne, Benjamin G Jones, Ashraf Muwafaq Flaiyah, Claudia Catani, Katie Dawson, Richard A Bryant, Carlijn de Roos, Verena Ertl, Edna B Foa, Julian D Ford, Eva Gilboa-Schechtman, Dunja Tutus, Katharin Hermenau, Tobias Hecker, Ole Hultmann, Ulf Axberg, Nasrin Jaberghaderi, Tine K Jensen, Silje M Ormhaug, Justin Kenardy, Ramon J L Lindauer, Julia Diehle, Laura K Murray, Jeremy C Kane, Kirsi Peltonen, Samuli Kangaslampi, Katy Robjant, Anke Koebach, Rita Rosner, Jaco Rossouw, Patrick Smith, Bruce J Tonge, Caitlin Hitchcock, Tim Dalgleish
Journal: The Lancet Child & Adolescent Health (2023)

Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators.
Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial
Authors: Qi Liu, Junqiang Chen, Yu Lin, Jinjun Ye, Wenbin Shen, Honglei Luo, Baosheng Li, Wei Huang, Shihong Wei, Jibin Song, Yaohui Wang, Huanjun Yang, Songtao Lai, Hongcheng Zhu, Dashan Ai, Yun Chen, Jiaying Deng, Shengnan Hao, Kuaile Zhao
Journal: The Lancet. Gastroenterology & hepatology (2023)
Upfront endoscopic necrosectomy or step-up endoscopic approach for infected necrotising pancreatitis (DESTIN): a single-blinded, multicentre, randomised trial
Authors: Ji Young Bang, Sundeep Lakhtakia, Shyam Thakkar, James L Buxbaum, Irving Waxman, Bryce Sutton, Sana F Memon, Shailendra Singh, Jahangeer Basha, Ajay Singh, Udayakumar Navaneethan, Robert H Hawes, Charles M Wilcox, Shyam Varadarajulu, Ji Young Bang, Shyam Varadarajulu, Bryce Sutton, Udayakumar Navaneethan, Robert Hawes, Charles Melbern Wilcox, Shyam Thakkar, Shailendra Singh, James Buxbaum, Irving Waxman, Ajay Singh
Journal: The Lancet. Gastroenterology & hepatology (2023)